Composition for eye wash

Abstract

To provide an eyewash composition that contains propylene glycol but yet has excellent antiseptic properties.SOLUTION: An eyewash composition contains 0.01 w / v% or more of at least one selected from the group consisting of hyaluronic acid and salts thereof and propylene glycol but does not contain an antiseptic agent selected from quaternary ammonium salt-based antiseptics, paraoxybenzoates, chlorobutanol, and sorbic acids.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an eyewash composition. [Background technology]

[0002] It is considered desirable to adjust the osmotic pressure of eyewashes to a value close to that of tears, and propylene glycol is often added as an isotonic agent. However, the addition of propylene glycol has the problem of deteriorating antiseptic properties. On the other hand, it is known that the use of preservatives such as benzalkonium chloride can improve antiseptic properties (Patent Document 1), but the use of preservatives is undesirable due to concerns about their effect on the cornea and their adsorption to contact lenses. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2012-167095 Summary of the Invention [Problem to be solved by the invention]

[0004] Therefore, the present inventors have an object to provide an eyewash composition that contains propylene glycol and yet has excellent antiseptic properties. [Means for solving the problem]

[0005] The present inventor has carried out intensive research in view of the above-mentioned problem, and has found that by using 0.01w / v% or more hyaluronic acid in combination with propylene glycol in eyewash composition, even though no preservative is compounded, or even though propylene glycol is compounded, eyewash composition can be given antiseptic properties.The present invention has been completed as a result of further research based on this finding, and is as follows: Item 1. An eyewash composition comprising (A) 0.01 w / v % or more of at least one selected from the group consisting of hyaluronic acid and its salts, and (B) propylene glycol, and not containing a preservative selected from the group consisting of a quaternary ammonium salt-based preservative, a parahydroxybenzoic acid ester, chlorobutanol, and a sorbic acid. Item 2. The eyewash composition according to Item 1, further comprising (C) 0.05 w / v % or more of at least one selected from the group consisting of edetic acid and salts thereof. Item 3. The eyewash composition according to Item 1 or 2, further comprising (D) at least one selected from the group consisting of pyridoxine, chondroitin sulfate, and salts thereof. Item 4. The eyewash composition according to any one of Items 1 to 3, which is used while wearing contact lenses. [Effects of the Invention]

[0006] By using at least one selected from the group consisting of hyaluronic acid and its salts in a concentration of 0.01 w / v% or more in combination with propylene glycol, an eyewash composition with excellent antiseptic properties can be provided, even without containing a preservative selected from quaternary ammonium salt-based preservatives, parahydroxybenzoic acid esters, chlorobutanol, and sorbic acids. DETAILED DESCRIPTION OF THE INVENTION

[0007] The embodiments included in the present disclosure are described in further detail below.

[0008] The present disclosure encompasses an eyewash composition that contains 0.01 w / v% or more of at least one selected from the group consisting of hyaluronic acid and its salts, and propylene glycol, but does not contain a preservative selected from quaternary ammonium salt-based preservatives, parahydroxybenzoic acid esters, chlorobutanol, and sorbic acids.

[0009] At least one selected from the group consisting of hyaluronic acid and its salts (sometimes referred to as component (A)) is a conventionally known substance, and examples of hyaluronic acid salts include alkali metal salts such as sodium salts. These may be used alone or in combination of two or more.

[0010] The content of component (A) in the eyewash composition of the present disclosure is not limited as long as it is 0.01 w / v% or more, and is preferably 0.01 to 0.08 w / v%, more preferably 0.01 to 0.02 w / v%, and even more preferably 0.015 to 0.02 w / v%.

[0011] Propylene glycol (sometimes referred to as component (B)) is conventionally known. The content of propylene glycol is not limited as long as the effects of the present disclosure are obtained, but is preferably 0.01 to 2 w / v%, more preferably 0.05 to 1.5 w / v%, and even more preferably 0.1 to 1 w / v% in the eyewash composition. The content of propylene glycol is also not limited as long as the effects of the present disclosure are obtained, but is preferably 1 to 100 parts by mass, more preferably 10 to 55 parts by mass, and even more preferably 20 to 50 parts by mass per part by mass of component (A) in the eyewash composition.

[0012] The eyewash composition of the present disclosure does not contain a preservative selected from quaternary ammonium salt-based preservatives, parahydroxybenzoic acid esters, chlorobutanol, and sorbic acids. These preservatives are conventionally known in the fields of eye drops and eyewashes. Examples of quaternary ammonium-based preservatives include benzalkonium chloride and benzethonium chloride. Examples of parahydroxybenzoic acid esters include parahydroxybenzoic acid esters such as methyl parahydroxybenzoate, propyl parahydroxybenzoate, and butyl parahydroxybenzoate, as well as salts of parahydroxybenzoic acid esters (e.g., alkali metal salts such as sodium salts). Examples of sorbic acids include sorbic acid and salts of sorbic acid (e.g., alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as calcium salts and magnesium salts).

[0013] The eyewash composition of the present disclosure may further contain at least one selected from the group consisting of edetic acid and its salts (sometimes referred to as component (C)). Edetic acid is also known as ethylenediaminetetraacetic acid (EDTA) and is conventionally known. Examples of salts of edetic acid include monosodium edetate, disodium edetate, trisodium edetate, tetrasodium edetate, dipotassium edetate, tripotassium edetate, and tetrapotassium edetate (including hydrates). These may be used alone or in combination of two or more.

[0014] When the eyewash composition of the present disclosure contains component (C), its content is not limited as long as the effects of the present disclosure are obtained, but the content of component (C) in the eyewash composition is, for example, 0.02 w / v% or more, preferably 0.05 w / v% or more, more preferably 0.05 to 0.1 w / v%, and even more preferably 0.05 to 0.08 w / v%. Furthermore, the content of component (C) is not limited as long as the effects of the present disclosure are obtained, but for example, it is preferably 1 to 8 parts by mass, more preferably 2 to 6 parts by mass, and even more preferably 2.5 to 5 parts by mass per part by mass of component (A) in the eyewash composition.

[0015] The eyewash composition of the present disclosure may further contain at least one selected from the group consisting of pyridoxine, chondroitin sulfate, and salts thereof (sometimes referred to as component (D)).

[0016] Pyridoxine and its salts are known substances and are not limited, but examples of pyridoxine salts include inorganic acid salts such as hydrochloride (pyridoxine hydrochloride) and phosphates.

[0017] Chondroitin sulfate is a mucopolysaccharide having a structure in which sulfate is ester-bonded to a sugar chain in which two sugars, D-glucuronic acid and N-acetylgalactosamine, are repeated. Examples of salts of chondroitin sulfate include, but are not limited to, alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as magnesium salt and calcium salt. Examples of salts of chondroitin sulfate include, but are not limited to, sodium chondroitin sulfate.

[0018] Although the chondroitin sulfate and salts thereof used in the present disclosure are not limited thereto, the molecular weight thereof is preferably, for example, about 5,000 to 45,000, more preferably about 10,000 to 40,000, and even more preferably about 15,000 to 30,000. The weight-average molecular weight is measured by gel filtration chromatography. Chondroitin sulfate and salts thereof are commercially available, for example, under the trade name "Extraneous Standard Sodium Chondroitin Sulfate" (Seikagaku Corporation, weight-average molecular weight 20,000).

[0019] Pyridoxine and its salts, and chondroitin sulfate and its salts may be used singly or in combination of two or more.

[0020] When the eyewash composition of the present disclosure contains component (D), its content is not limited as long as the effects of the present disclosure are obtained, but the content of component (D) in the eyewash composition is preferably 0.001 to 0.1 w / v%, more preferably 0.01 to 0.07 w / v%, and even more preferably 0.04 to 0.06 w / v%. The content of component (D) is also not limited as long as the effects of the present disclosure are obtained, but it is preferably 1 to 10 parts by mass, more preferably 2 to 6 parts by mass, and even more preferably 2 to 4 parts by mass per part by mass of component (A) in the eyewash composition.

[0021] Furthermore, although not limiting the present disclosure, more preferably, at least one selected from the group consisting of pyridoxine and its salts is present in the eyewash composition at a concentration of 0.008 to 0.01 w / v%, even more preferably 0.001 to 0.01 w / v%, and particularly preferably 0.005 to 0.01 w / v%.

[0022] Furthermore, although not limiting the present disclosure, more preferably, at least one selected from the group consisting of chondroitin sulfate and its salts is present in the eyewash composition at 0.0055 to 0.05 w / v%, even more preferably 0.01 to 0.05 w / v%, and particularly preferably 0.025 to 0.05 w / v%.

[0023] The eyewash composition of the present disclosure may further contain any other component acceptable for use in eye drops or eyewashes. Examples of such other components include, but are not limited to, buffers, stabilizers, isotonicity agents, solvents (e.g., water), pH adjusters, medicinal ingredients, cooling agents, irritants, thickeners, etc. The other components may be selected appropriately depending on the purpose, etc., as long as they do not impair the effects of the present disclosure. They may be used alone or in combination with two or more other components, and the amounts of each may be determined appropriately. Note that, although the components (A) to (D) are also known as medicinal ingredients, stabilizers, thickeners, etc., depending on the component, the components (A) to (D) are not included in the optional other components of the present disclosure.

[0024] Examples of such other components include buffers, such as boric acid and borax. The buffers may be used singly or in combination of two or more. For example, when the composition contains boric acid, the content of boric acid is not limited as long as it does not impair the effects of the present disclosure, and is preferably 0.1 to 2.5 w / v%, and more preferably 0.5 to 2 w / v% in the composition. For example, when the composition contains borax, the content of borax is not limited as long as it does not impair the effects of the present disclosure, and is preferably 0.005 to 0.5 w / v%, and more preferably 0.005 to 0.05 w / v% in the composition. The composition may or may not contain a buffer other than boric acid and borax. Alternatively, the composition may contain only either boric acid or borax.

[0025] Examples of such other components include stabilizers, such as polysorbates (polysorbate 80, polysorbate 60, etc.), polyoxyethylene (POE) hydrogenated castor oil (POE(80) hydrogenated castor oil, POE(60) hydrogenated castor oil, etc.; the number in parentheses indicates the average number of moles of ethylene oxide added), POE polyoxypropylene glycol, and trometamol. These may be used alone or in combination of two or more. When the composition contains a stabilizer, the content thereof is not limited as long as it does not impede the effects of the present disclosure, and is preferably 0.01 to 1 w / v % and more preferably 0.05 to 0.1 w / v % in the composition. When the composition contains a stabilizer, it may contain only one or only two selected from, for example, polysorbate, POE hydrogenated castor oil, POE polyoxypropylene glycol, and trometamol. Also, when the composition contains, for example, polysorbate, it can be prepared without blending POE hydrogenated castor oil, POE polyoxypropylene glycol, and / or trometamol.

[0026] Examples of such other ingredients include medicinal ingredients such as amino acids, anti-inflammatory agents, vitamins, antihistamines, etc. These may be used alone or in combination of two or more.

[0027] Although not limiting the present disclosure, examples of amino acids include amino acids and their salts, such as glutamic acid and its salts; and amino acid analogs, such as taurine. These may be used alone or in combination of two or more. The eyewash composition of the present disclosure can also be prepared without adding an amino acid and / or a salt thereof. The amino acid here refers to an amino acid that can be a structural unit of a protein and has both an amino group and a carboxyl group, and includes, for example, L-aspartic acid. The eyewash composition of the present disclosure can also be prepared without adding an amino acid analog.

[0028] Although not limiting the present disclosure, examples of anti-inflammatory agents include zinc sulfate, zinc lactate, epsilon-aminocaproic acid, allantoin, glycyrrhizic acid and its salts, and azulenes (azulene, dimethylisopropylazulene, dimethylethylazulene, salts thereof, etc.). These may be used alone or in combination of two or more. Although not limiting the present disclosure, the composition preferably does not contain zinc sulfate and / or zinc lactate. The composition can also be prepared without incorporating epsilon-aminocaproic acid, allantoin, glycyrrhizic acid, and its salts.

[0029] Although not limiting the present disclosure, examples of vitamins include vitamin A (retinol palmitate, retinol acetate, retinol, retinal, retinoic acid, etc.), vitamin B (flavin adenine dinucleotide, cyanocobalamin, etc.), vitamin E (tocopherol acetate, tocopherol succinate, tocopherol nicotinate, tocopherol linoleate, etc.). These may be used alone or in combination of two or more. Although not limiting the present disclosure, the composition may also be prepared without blending at least one of the vitamins.

[0030] Although not limiting the present disclosure, examples of antihistamines include chlorpheniramine and its salts (e.g., chlorpheniramine maleate), diphenhydramine and its salts (e.g., diphenhydramine hydrochloride), etc. These may be used alone or in combination of two or more. The composition of the present disclosure can also be prepared without incorporating an antihistamine.

[0031] When the composition of the present disclosure contains a medicinal ingredient, the content of the medicinal ingredient is not limited as long as it does not interfere with the effects of the present disclosure. The content of the medicinal ingredient in the composition is preferably 0.05 to 0.3 w / v%, more preferably 0.1 to 0.3 w / v%, and even more preferably 0.2 to 0.27 w / v%, for example.

[0032] Examples of the other component include a cooling agent, such as menthol, camphor, or borneol. The cooling agent may be used alone or in combination of two or more. The composition of the present disclosure may contain a cooling agent, or may be prepared without adding a cooling agent.

[0033] An example of such other component is a stimulant, and examples of the stimulant include aldehydes such as propionaldehyde. Without limiting the present disclosure, the composition of the present disclosure may contain a stimulant, or may be prepared without blending a stimulant.

[0034] Examples of such other components include thickeners, such as alginic acid and its salts, hydroxyethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymers, salts thereof, and glycerin. These may be used alone or in combination of two or more. The eyewash composition of the present disclosure can also be prepared without blending these thickeners.

[0035] The eyewash composition of the present disclosure can be produced by mixing the components (A) and (B), and, if necessary, the components (C) and (D), and the other components. The mixing method is not limited as long as these components can be mixed, and they may be mixed according to a conventional procedure.

[0036] The pH of the eyewash composition of the present disclosure is not limited as long as it is within a range that can be used as an eye drop or eyewash, but examples of such a pH include pH 5 to 8 at room temperature (25°C), preferably pH 5.5 to 6.5, more preferably pH 5.5 to 6, and even more preferably pH 5.5 to 5.8.

[0037] The eyewash composition of the present disclosure is in liquid form at room temperature, and its method of use is not limited as long as it can cleanse the eyes in the same manner as conventionally known methods.It is typically used for eyewashing using an eyewash cup (eyecup) or by eye drops.

[0038] The eyewash composition of the present disclosure may be used with or without contact lenses, regardless of whether they are hard or soft contact lenses.

[0039] The eyewash composition of the present disclosure is not limited as long as it can be used as described above, but when used in an eyewash cup, it is usually placed in a conventionally known general eyewash container (including, for example, a container body and a cap). The volume of the container is also not limited, but from the viewpoint of ease of use, the volume is preferably, for example, 450 to 550 mL.

[0040] Eye washing using an eyewash cup can be done according to the usual procedure, for example, by pouring an appropriate amount of the eyewash composition of the present disclosure from the container into the eyewash cup, for example, 4 to 6 mL per eye at a time, then pressing the cup against the area around one eye to bring the eyewash composition in the cup into contact with the eye, and blinking several times.

[0041] Furthermore, when the eyewash composition of the present disclosure is used for eyewashing by instillation, it is usually contained in an eyedropper container. The eyedropper container is not limited as long as it can contain the composition and be used for instillation, and examples thereof include eyedropper containers used for conventionally known eyedrops and eyedrop-type eyewashes (for example, types in which at least two of the container body, inner stopper (nozzle), and cap are integrated). The volume of the container is not limited, but from the viewpoint of ease of use, a volume of 8 to 20 mL is exemplified.

[0042] Eyewashing by instillation can be performed according to the usual method, by instilling 4 to 6 drops of the eyewash composition of the present disclosure per eye at a time. There are no limitations on the amount of each drop, but a preferred amount is 35 to 40 μL per drop, for example.

[0043] According to the eyewash composition of the present disclosure, although it does not contain a preservative selected from quaternary ammonium salt-based preservatives, parahydroxybenzoates, chlorobutanol, and sorbic acids, it can be provided with excellent antiseptic properties by combining 0.01 w / v% or more of at least one selected from the group consisting of hyaluronic acid and its salts with propylene glycol. Furthermore, by further incorporating at least one selected from the group consisting of edetic acid and its salts, or at least one selected from the group consisting of pyridoxine, chondroitin sulfate, and their salts, it can be provided with even more excellent antiseptic properties, as shown in the examples below, even though it does not contain a preservative. Furthermore, if the composition further contains the aforementioned medicinal ingredients, it can also achieve useful effects based on the medicinal ingredients. [Example]

[0044] The present disclosure will be described in more detail below with reference to examples, but the present disclosure is not limited thereto.

[0045] Test Example 1. Preparation of eyewash composition The components were mixed according to the blending ratios shown in Table 1 below, and the resulting mixtures were passed through a sterilizing filter (Examples 1 to 5, Reference Example, Comparative Examples 1 to 3). The pH of each composition was measured immediately after preparation. The pH was measured at room temperature (25°C) using a tabletop pH meter F-52 (manufactured by Horiba, Ltd.). The sodium chondroitin sulfate ester in the table was non-standard sodium chondroitin sulfate (weight average molecular weight 20,000).

[0046] 2. Antiseptic power evaluation <Candida> Candida albicans was suspended in sterile saline to prepare a bacterial suspension (1 × 10 8 cfu / mL) was prepared. 10 mL of each composition obtained as described above was added to the bacterial solution at 1 × 10 6 The compositions were inoculated to a concentration of 0.1 cfu / mL and stored at 30°C in a dark place for 14 days. After storage, 0.1 mL of each composition inoculated with Candida was applied to a commercially available GPLP agar medium (GPLP agar medium "Daigo", manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) using a colony-raising stick. After 48 hours of incubation at 30°C, the number of colonies was visually counted, and the counted value multiplied by 100 was used as the bacterial count for each composition after 14 days of storage. The bacterial count at the time of inoculation was defined as 100%, and the percentage of bacterial count (survival rate) for each composition after 14 days of storage was calculated. The antiseptic power of the eyewash composition was evaluated from the calculated values ​​according to the following criteria. [Evaluation criteria] ◎: The survival rate is reduced to 0.1% or less of the inoculated amount ○: The survival rate is reduced to less than 1% of the inoculum amount. △: The survival rate decreased to 10% or less of the inoculated amount ×: Does not meet the above △ criteria

[0047] <Staphylococcus aureus> Staphylococcus aureus was suspended in sterile saline to prepare a bacterial suspension (1 × 10 8 cfu / mL) was prepared. 10 mL of each composition obtained as described above was added to the bacterial solution at 1 × 10 6 The compositions were inoculated to a concentration of 0.1 cfu / mL and stored at 35°C in a dark place for 14 days. After storage, 0.1 mL of each composition inoculated with Staphylococcus aureus was applied to a commercially available SCDLP agar medium (SCDLP agar medium "Daigo", manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) using a colony-raising stick. After culturing at 35°C for 48 hours, the number of colonies was visually counted, and the counted value multiplied by 100 was used as the bacterial count for each composition after 14 days of storage. The bacterial count at the time of inoculation was set at 100%, and the percentage of bacterial count (survival rate) for each composition after 14 days of storage was calculated. The antiseptic power of the eyewash composition was evaluated from the calculated value according to the same criteria as described above.

[0048] 3.Results The results are shown in Tables 1 and 2.

[0049] [Table 1]

[0050] [Table 2]

[0051] The reference example containing the preservative benzalkonium chloride was the positive control in this test example, and as shown in Table 1, the evaluation result was ⊚, indicating excellent preservative power. In contrast, Comparative Example 1, which did not contain benzalkonium chloride but contained propylene glycol, was evaluated as ×, indicating that the desired preservative power was not achieved. Furthermore, Comparative Example 2, which did not contain benzalkonium chloride or propylene glycol but contained 0.01 w / v% sodium hyaluronate, was evaluated as △, indicating that the desired preservative power was not achieved. Furthermore, Comparative Example 3, which did not contain benzalkonium chloride but contained 0.001 w / v% sodium hyaluronate and propylene glycol, was evaluated as △, indicating that the desired preservative power was not achieved.

[0052] On the other hand, in Example 1, which does not contain benzalkonium chloride and contains 0.01 w / v% sodium hyaluronate and propylene glycol, the evaluation result is ○, and the antiseptic effect is confirmed to be improved.In Example 2, which contains an increased amount of sodium hyaluronate compared to Example 1, the evaluation result is also ○, and the antiseptic effect is confirmed to be improved.From this, it is surprisingly confirmed that by combining propylene glycol, which has poor antiseptic properties, with 0.01 w / v% or more sodium hyaluronate, the antiseptic effect of the eyewash composition can be improved.

[0053] Furthermore, the evaluation results were also good or excellent, and improved preservative properties were observed in Examples 3 to 5, in which sodium edetate was further blended in Examples 1 and 2, Example 6, in which sodium chondroitin sulfate was further blended in Example 5, and Example 7, in which pyridoxine hydrochloride was further blended in Example 6. Furthermore, when the pH of Examples 1 to 7 was set to 6.2, improved preservative properties were observed to the same extent as in Examples 1 to 7.

[0054] From these findings, it was confirmed that the antiseptic properties of the eyewash composition can be improved by combining propylene glycol, which has poor antiseptic properties, with sodium hyaluronate at 0.01 w / v% or more, and further by combining sodium edetate, sodium chondroitin sulfate, or pyridoxine hydrochloride.In addition, the eyewash compositions of Examples 1 to 7 can improve their antiseptic properties without using preservatives such as benzalkonium chloride, which may be adsorbed onto contact lenses, so that they can be used to wash eyes while wearing contact lenses.

[0055] Prescription example Eyewash compositions were prepared according to the formulation ratios shown in Table 3, and their preservative properties were evaluated in the same manner as in the test examples.When all of the eyewash compositions in Formulation Examples 1 to 7 showed improved preservative properties to the same extent as in Example 7,

[0056] [Table 3]

Claims

1. (A) 0.01 w / v% or more of at least one selected from the group consisting of hyaluronic acid and salts thereof; (B) propylene glycol, and (C) 0.05 w / v% or more of at least one selected from the group consisting of edetic acid and its salts and does not contain a preservative selected from quaternary ammonium salt-based preservatives, parahydroxybenzoic acid esters, chlorobutanol, and sorbic acids.

2. The eyewash composition according to claim 1, further comprising (D) at least one selected from the group consisting of pyridoxine, chondroitin sulfate, and salts thereof.

3. The eyewash composition according to claim 1 or 2, which is used while wearing contact lenses.

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